Grass Pollen Tablets Research Articles

Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy.

IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen-specific IgG2levels after a 3rd consecutive pre-seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen-specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM-AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders. Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae-specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub-group of individuals enrolled in a randomized, double-blind, placebo-controlled, sublingual AIT study evaluating the safety and efficacy of a 300IR HDM tablet. After 1-year sublingual AIT, HDM-specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM-specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM-AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM-specific IgG2 and IgE responses is only observed in individuals stratified as high responders. We provide evidence for coordinated serum immune responses upon AIT in HDM-allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM-specific IgE, IgG2, and IgG4 in serum could be used as follow-up combined markers to support decision as to AIT continuation and/or adaptation.

Efficacy of sublingual immunotherapy tablets in dust mite and pollen allergy.

The latest evidence on the mechanisms, efficacy, and safety of sublingual immunotherapy (SLIT) was reviewed. Interleukin (IL) 35 and IL-35-producing regulatory T cells were assessed as new biomarkers for SLIT responsiveness. A detailed analysis of clinical studies, including timothy grass pollen, 5-grass pollen, ragweed, and house-dust mite SLIT tablets, was provided, including a comparative analysis of efficacy and safety of SLIT versus subcutaneous immunotherapy.

Real-life safety of 5-grass pollen tablet in 5-to-9-year-old children with allergic rhinoconjunctivitis

BackgroundAlthough 5-grass pollen sublingual immunotherapy has a good safety profile in controlled clinical trials, additional safety information among pediatric patients in a real-world setting would be useful. ObjectiveTo further document the safety of 5-grass tablet among children aged 5 to 9 years with allergic rhinoconjunctivitis (ARC). MethodsThis multicenter, observational study included allergy immunotherapy-naïve 5- to 9-year-old children with grass pollen–induced ARC prescribed with 5-grass tablet daily (3-day dose escalation to 300 index of reactivity [IR]). Patients were followed up daily for safety and tolerability over the first 30 treatment days. Adverse events (AEs) and adverse drug reactions (ADRs) were analyzed descriptively. ResultsThree hundred seven children (mean age, 7.1 years) were enrolled. Fifty-eight percent were confirmed as polysensitized, and 36% had mild-to-moderate asthma. Of 307 patients, 233 (76%) reported AEs, and 173/307 (56%) reported ADRs, most frequently mild application-site reactions (throat irritation, oral pruritus, oral paresthesia). Sixteen of 307 (5.2%) patients withdrew because of ADRs. In 143 of 173 (83%) patients, ADRs first occurred within 1 week of starting treatment. More than half of the ADRs lasted less than 2 days, and ADRs resolved spontaneously in 161 of 173 (93%) patients. Recurrences of ADRs were reported in 45 of 173 (26%) patients and were also mainly application-site reactions. No notable differences were found in ADRs related to whether patients had asthma at inclusion. Neither epinephrine use nor admission to intensive care unit was reported. ConclusionThe safety profile of 5-grass tablet in pediatric ARC patients aged 5 to 9 years was consistent with safety findings in older patients, most ADRs being at the application site and mild to moderate. ClinicalTrials.gov identifier: NCT02295969; EUPAS registration number: 8104.

Immunotherapy with grass pollen tablets reduces medication dispensing for allergic rhinitis and asthma: A retrospective database study in France.

Moderate-to-severe allergic rhinitis (AR) may increase the risk of developing or worsening asthma, whereas treatment of AR with subcutaneously or sublingual allergen immunotherapy (SLIT) may slow this progression. In a retrospective real-world analysis, prescription fulfilment data were gathered from French retail pharmacies between 1 March 2012 and 31 December 2016. Using linear regression analyses, patients having received at least two prescriptions of grass pollen SLIT tablets over at least 2 successive years were compared with control patients having received symptomatic medications only. A total of 1099 SLIT patients and 27475 control patients were included in the main analysis. With regard to symptomatic AR medication dispensing, we observed a 50% decrease in the pre-index/follow-up ratio in the SLIT group, a 30% increase in the control group without age matching (P<0.0001 vs SLIT) and a 20% increase in the control group with age matching (P<0.0001 vs SLIT). During the follow-up, 11 (1.8%) and 782 (5.3%) patients initiated asthma treatment in the SLIT and control groups, respectively. The relative risk of medication dispensing for new asthma was lower in the SLIT group (by 62.5% [29.1%-80.1%] without age matching (P=0.0025) and by 63.7% [31.5%-80.7%] with age matching; P=0.0018). SLIT was also associated with slower progression of asthma medication dispensing during the follow-up period, relative to the control group (regression coefficient: -0.58 [-0.74 to 0.42] without age matching (P<0.0001) and -0.61 [-0.76 to -0.46] with age matching; P<0.0001). Prescription of grass pollen SLIT tablets reduced the dispensing of AR and asthma medications in real life.

Two grass pollen tablets commercially available for allergy immunotherapy display different IgE epitope repertoires

BackgroundThe distribution of Pooideae species varies across Europe. Especially, Timothy is less represented in Southern than in Northern Europe. Since allergenic cross-reactivity between pollens from different grasses is only partial, grass pollen-allergic patients are expected to display different sensitization profiles, with specific IgE directed against different combinations of allergenic epitopes, depending on their living places in Europe and the grasses they are exposed to. In this context, this study aimed at comparing two tablets commercially available for allergy immunotherapy, namely a 5-grass (Cocksfoot, Meadow-grass, Rye-grass, Sweet vernal-grass and Timothy) and a 1-grass (Timothy) pollen tablets, for their ability to represent the sensitization profiles of patients, depending on whether they live in Southern or Northern Europe.MethodsSera were collected from adult patients living in Spain (n = 19) and Sweden (n = 22). Tablets were compared for their ability to inhibit the binding of patient serum IgE to pollen allergens from twelve grasses commonly distributed throughout Europe, as determined by the areas under the curves obtained by ELISA-inhibition. Tablets were adjusted to an equivalent allergenic activity, based on the CBER/FDA bioequivalent allergy unit.ResultsInhibition of the IgE binding to pollen allergens from twelve grasses was significantly stronger with the 5-grass than with the 1-grass pollen tablet (p < 0.0001), regardless of whether patients were considered as a whole or by geographical area. This difference between tablets was significantly greater for Southern than Northern European patients (p < 0.05).ConclusionsCompared to the 1-grass tablet, the 5-grass tablet generally covers better the sensitization profiles of European patients, especially patients from Southern Europe, in principle less exposed to pollen from Timothy than from other grasses. The 5-grass tablet is therefore expected to elicit larger spectra of blocking antibodies, which might have implications in light of the generally accepted mechanisms of allergy immunotherapy.

PEDIATRIC OBSERVATIONAL STUDY OF 300IR 5-GRASS TABLET IN GRASS POLLEN–INDUCED ALLERGIC RHINOCONJUNCTIVITIS: FURTHER SAFETY DATA

Introduction We report further safety data from a European post-marketing study of 300IR 5-grass pollen tablet* in grass pollen–allergic children. Methods Immunotherapy-naïve children (5-9 years) with grass pollen–induced allergic rhinitis (GP-AR) with/without conjunctivitis were prescribed 300IR tablet daily (3-day dose escalation) in this multicenter observational study (NCT02295969). After informed consent, patients were followed-up over the first 30 treatment days. Adverse drug reactions (ADRs) were analyzed descriptively. Results 307 children (mean age: 7.1 years) were enrolled. As previously reported, 173/307 (56%) patients had ADRs (generally application-site reactions) during the first treatment month. Of these 161/173 (93%) resolved spontaneously. In 143/173 (83%) patients, ADRs first occurred within one week of starting treatment. The median time to onset of most common ADRs was 3.0 days. Throat irritation, oral pruritus, and oral paresthesia occurred 2.5, 2.0, and 2.0 days (respective medians) following initiation. Median duration of ADRs arising within the first 24 hours was 4.7 days. ADR recurrences were reported in 45/173 (26%) patients. These were most frequently throat irritation (in 21/173 [12%]), oral paresthesia (in 9/173 [5%]) and tongue pruritus (in 6/173 [3.5%]) which resolved shortly after starting (median duration of 1 day, 2 days, and 4 hours, respectively). Conclusions Over the first treatment month for this pediatric GP-AR population, ADRs presented in approximately half of the patients, occurred within a few days after starting treatment, and generally resolved within a week. ADR recurrences were reported in approximately a quarter of the patients. We report further safety data from a European post-marketing study of 300IR 5-grass pollen tablet* in grass pollen–allergic children. Immunotherapy-naïve children (5-9 years) with grass pollen–induced allergic rhinitis (GP-AR) with/without conjunctivitis were prescribed 300IR tablet daily (3-day dose escalation) in this multicenter observational study (NCT02295969). After informed consent, patients were followed-up over the first 30 treatment days. Adverse drug reactions (ADRs) were analyzed descriptively. 307 children (mean age: 7.1 years) were enrolled. As previously reported, 173/307 (56%) patients had ADRs (generally application-site reactions) during the first treatment month. Of these 161/173 (93%) resolved spontaneously. In 143/173 (83%) patients, ADRs first occurred within one week of starting treatment. The median time to onset of most common ADRs was 3.0 days. Throat irritation, oral pruritus, and oral paresthesia occurred 2.5, 2.0, and 2.0 days (respective medians) following initiation. Median duration of ADRs arising within the first 24 hours was 4.7 days. ADR recurrences were reported in 45/173 (26%) patients. These were most frequently throat irritation (in 21/173 [12%]), oral paresthesia (in 9/173 [5%]) and tongue pruritus (in 6/173 [3.5%]) which resolved shortly after starting (median duration of 1 day, 2 days, and 4 hours, respectively). Over the first treatment month for this pediatric GP-AR population, ADRs presented in approximately half of the patients, occurred within a few days after starting treatment, and generally resolved within a week. ADR recurrences were reported in approximately a quarter of the patients.

Preventing new sensitization and asthma onset by allergen immunotherapy: the current evidence.

Specific allergen immunotherapy is considered a key candidate for a successful preventive intervention in atopic diseases. The strong association of atopic manifestations such as rhinitis and asthma with atopic sensitizations (specific serum IgE) provide a rationale for early intervention in childhood and adolescence. Currently, the documentation of the disease-modifying intervention effects is limited to the secondary prevention of asthma symptoms in children with allergic rhinoconjunctivitis. These effects appear to be rather allergen specific than nonspecific. Documentation on disease modification including a reduction of asthma symptoms in children, particularly with grass pollen tablets has become quite robust. It is not clear up to now, if the new onset of allergic sensitizations can be modified. So far data on primary prevention are not conclusive.

A survey on the perception of allergy specialists about the reimbursed grass pollen tablets for seasonal allergic rhinitis in Italy

BackgroundSublingual immunotherapy (SLIT) is a feasible option to classical subcutaneous immunotherapy to treat respiratory allergy and is increasingly prescribed in Europe. However, the lack of reimbursement may limit its prescription. In 2015, the 5-grass pollen tablets was authorized by the European Medicine Agency to treat grass-pollen induced rhinitis and was approved in Italy for full reimbursement. We evaluated the opinions of allergy specialists after the availability of the reimbursed 5-grass pollen tablets.MethodsA multiple choice questionnaire composed by six questions was used to assess the specialists opinion. The questionnaire was uploaded on the free access online platform SurveyMonkey. The link to access the platform was sent to all members of the Società Italiana di Asma, Allergologia e Immunologia Clinica (SIAAIC). The access to the questionnaire was anonymous. At survey ending, the access was closed and data were downloaded directly from SurveyMonkey website.ResultsThe questionnaire was filled by 70 allergists. The majority of allergists felt as most important the concept of SLIT as a drug, the content of allergen extract mirroring the natural exposure, the pre-coseasonal schedule as the most patient’s oriented, the very good profile of tolerability and safety, the importance of the build-up phase, and the importance of checking the patient after starting immunotherapy.ConclusionsThe opinions of the Italian allergy specialists about the reimbursed 5-grass-pollen tablets are very positive and make likely an appropriate prescription of SLIT for grass-pollen induced rhinitis in the next years.

Safety Review of 5-Grass Pollen Tablet from Pooled Data of Clinical Trials

The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma. To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials. Subjects (5-65 years old) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies. Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists could participate. Randomized subjects received a 5-grass or placebo tablet daily 2 or 4 months preseasonally and coseasonally (5single-season studies, over 3 years in a long-term study) or outside the season (phase I studies). Adverse events were pooled and analyzed descriptively. Among 2,512 subjects enrolled, 1,514 received the 5-grass tablet. A total of 1,038 adults and 154 pediatric (5-17years old) subjects were treated with the 300 Index of Reactivity dose (vs 840 and 158 placebo recipients, respectively); 17% had intermittent asthma, and 62% were polysensitized. Adverse reactions (ADRs) reported in more than 10% of actively treated subjects were mild or moderate application-site reactions, for example, oral pruritus 25% (placebo 4%) and throat irritation 21% (placebo 3%). These generally occurred during the first week of treatment and decreased over time. They led to discontinuation in less than 2.5% of subjects. None of the 3serious ADRs were reports of anaphylaxis. No notable differences were detected in terms of incidence, nature, and severity of ADRs between adult and pediatric populations, nor between subjects with or without asthma. The pooled analysis in 1,514 subjects from 8 clinical studies demonstrates that the 5-grass pollen sublingual tablet has a similar good safety profile in adult and pediatric patients with or without mild, intermittent asthma.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression.

IntroductionMicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome.MethodUsing specific culture conditions, we differentiated immature human monocyte‐derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of TH1, TH2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non‐allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months.ResultsWe successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR‐132 and miR‐155), was down‐regulated compared to non‐allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy.ConclusionsStudying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow‐up AIT efficacy.

Management of Grass Pollen Allergy with 5-Grass Pollen Tablet: Results of a 2-Year Real-Life Study.

IntroductionAllergen immunotherapy is the only treatment option for allergic rhinitis with disease-altering potential. It was the objective of this study to assess the effectiveness and tolerability of a 5-grass pollen tablet in a large population of non-selected grass pollen allergic patients, i.e. patients with different clinical profiles in daily clinical practice.MethodsIn a 2-year, prospective, open-label, multicenter, non-controlled, observational study patients were included from 327 centers across Germany. Rhinoconjunctivitis symptoms, symptomatic medication intake and adverse events were recorded.ResultsA total of 1482 patients aged 4–75 years were included. During the 2-year period of 5-grass pollen tablet therapy, mean rhinoconjunctivitis score decreased significantly in the overall study population by 65.5% (P < 0.001). The percentage of patients taking symptomatic medication decreased from 83.8% to 42.7%. Mean 2-year improvements in rhinoconjunctivitis scores and decreases in the percentage of patients taking symptomatic medication were broadly similar in adults, adolescents and children, in patients with polyallergy versus monoallergy, and in patients with/without asthma. Among polyallergic patients, concomitant application of another specific immunotherapy did not impair treatment outcomes. Adverse drug reactions, predominantly affecting the local application area, occurred in 15.4% of the overall patient population (n = 229). No cases of anaphylaxis or epinephrine use were documented.ConclusionThis study indicates that sublingual immunotherapy with the 5-grass pollen tablet is well tolerated and provides sustained effectiveness over 2 years in patients with different clinical profiles, producing a significant decrease in allergic symptoms and a reduction in the use of symptomatic medication.FundingStallergenes GmbH.

Comparison of scores associating symptoms and rescue medication use for evaluating the efficacy of allergy immunotherapy in seasonal allergic rhinoconjunctivitis: results from five trials.

Over the past decade, regulatory bodies and scientific societies recommended, as primary efficacy outcome, a score that reflects both symptom severity and use of rescue medication for clinical trials in allergy immunotherapy (AIT). We sought to compare the results obtained with two subject-specific scores, the Combined Score (CS) and the Adjusted Symptom Score (AdSS), for assessment of AIT in seasonal allergic rhinoconjunctivitis due to birch and grass pollen allergens. CS and AdSS were evaluated in subjects receiving a 300IR dose of allergen extract daily, by sublingual route, in four clinical trials with the 5-grass pollen tablet (NCT00367640, NCT00409409, NCT00955825 and NCT00418379) and one with the birch pollen solution (NCT01731249). The CS is derived from the Rhinoconjunctivitis Total Symptom Score (RTSS) and the Rescue Medication Score (RMS) giving equal weight to symptoms and medication use. The AdSS is a symptom score adjusting for rescue medication use. Efficacy end-points were analysed using an analysis of covariance linear model. In all trials, despite the different constructs of the two scores, Combined Score or Adjusted Symptom Score were similarly reduced in the 300IR group compared to the placebo group. Treatment effect was consistently demonstrated with both scores, CS and AdSS, used as either daily scores or average of the daily scores over the pollen season. Minor differences with the same statistical conclusions were observed between the results, leading to the same interpretation. The two scores, combined and adjusted scores, for evaluation of clinical efficacy of AIT have led to similar results, with similar statistical conclusions and similar interpretation.

P061 Post-marketing safety experience with 300IR 5-grass pollen tablet for allergic rhinoconjunctivitis

P061 Post-marketing safety experience with 300IR 5-grass pollen tablet for allergic rhinoconjunctivitis

Persistence of treatment with 5-grass pollen tablets in patients with allergic rhinitis: a real-life study

BackgroundIn patients with allergic rhinitis, treatment adherence to allergen immunotherapy varies greatly in randomized and real-life studies. ObjectiveTo evaluate the use of a 5-grass pollen tablet as sublingual immunotherapy, its treatment persistence, and the reasons for discontinuation in a real-life clinical setting. MethodsThis multicenter, prospective, open-label, noncontrolled observational study evaluated the use of sublingual immunotherapy with a 5-grass pollen tablet in a cross-sectional population of patients (≥5 years old) with grass pollen-induced allergic rhinitis with or without asthma. The primary objective was to determine the percentage of patients persisting with treatment across 1 season in a pre–co-seasonal scheme. Secondary objectives included evaluation of reasons for treatment discontinuation, safety and adverse events; effectiveness (based on physician and patient assessments), and treatment compliance. ResultsThe study included 196 patients (49.2% male, mean age 27.5 years, range 5.3–65.7 years), with treatment provided by 47 participating physicians. Sixty-seven percent of patients had polysensitivity and 32% had coexistent asthma. On average, patients were treated for 7 months with the 5-grass pollen tablet. After 1 month, 85% of all patients persisted with treatment, and 70% persisted after 7 months. Treatment discontinuation was due chiefly to known side effects (mild to moderate local allergic reactions). Most patients reported symptom improvement; 80% of all patients intended to continue treatment next season. ConclusionMost patients with allergic rhinitis treated pre–co-seasonally with a 5-grass pollen tablet persisted with treatment after the first pollen season. Patients were willing to continue their treatment in the following season owing to improvement of symptoms.

A major step forward for sublingual immunotherapy: the quality of 5-grass pollen tablet is recognized also in Italy.

A major step forward for sublingual immunotherapy: the quality of 5-grass pollen tablet is recognized also in Italy.

Clinical Outcome and Tolerability of a 2-Year Sublingual Allergen Immunotherapy (AIT) with a 5-Grass Pollen Tablet in Polyallergic Patients – Real-Life Medical Practice Data

Patients with respiratory allergies are often polyallergic, i.e. allergic to more than one allergen. Clinical trials have shown that these patients can effectively and safely be treated with AIT, however data from real-life medical practice remain scarce.

Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2years after treatment cessation, as measured by a recommended daily combined score.

BackgroundThe 300IR (index of reactivity) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here, we report maintenance of efficacy and safety over 2 years following treatment discontinuation.MethodsRandomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 trial in patients aged 18–50 years with ARC. During study years 1–3, patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo, according to a discontinuous pre- and coseasonal protocol. Study years 4 and 5 were treatment-free. In response to health authorities’ recommendations, the daily combined score (DCS) was assessed in a post-hoc analysis as the efficacy endpoint. Components of the DCS were daily rhinoconjunctivitis total symptom score (DRTSS) and daily rescue medication score (DRMS).Results633 patients with ARC were randomized to placebo (n = 219) or 300IR 5-grass pollen tablet, beginning 4 months (4 M, n = 207) or 2 months (2 M, n = 207) prior to the estimated start of the grass pollen season and continuing until season’s end. During the first post-treatment year, a statistically significant difference versus placebo in least squares (LS) mean DCS was noted in patients previously receiving active treatment (300IR (2 M) point estimate: −0.16, 95% confidence interval (CI95%): [−0.26, −0.06], p = 0.0019; −31.1%; 300IR (4 M) point estimate: −0.13, CI95%: [−0.23, −0.03], p = 0.0103, −25.3%). During the second post-treatment year, patients in the 300IR (4 M) group, but not the 300IR (2 M) group, showed a statistically significant difference in LS mean DCS versus placebo (point estimate: −0.11, CI95%: [−0.21; 0.00], p = 0.0478, −28.1%). This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment. A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years (except for DRTSS in year 5). In the absence of any active treatment, the safety profile was similar in the active groups versus placebo group during either post-treatment year.ConclusionsIn adults with grass pollen-associated ARC, 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season’s end demonstrated efficacy across all variables during active treatment, and this effect was prolonged for up to 2 years post-treatment.Trial registrationClinicalTrials.gov identifier: NCT00418379.

The relative clinical impact of sublingual immunotherapy with carbamylated monomeric allergoids on allergic respiratory symptoms

Background To assess the cumulative and allergen-specific magnitude of effect, and its relative clinical impact, of sublingual allergy immunotherapy with carbamylated monomeric allergoids for allergic rhinoconjunctivitis. Carbamylated allergoids are hypoallergenic extracts with enhanced bioavailability, consequent to a partial resistance to enzymatic degradation, providing efficient dose-tuning. Methods Literature was searched for double-blind placebo-controlled randomized trials administering this treatment, without any restrictions. Pooled analysis of the effects on total symptoms scores (TSSs) during the first season of treatment was performed and for each selected trial the relative clinical impact (RCI) was calculated as the percentage reduction in TSSs obtained with active treatment compared to placebo. The effect size (SMD), the overall and allergen-related RCI were used to estimate an indirect comparison with pharmacotherapy (based on summary data recently extracted from literature). Results Eight studies (4 in grass, 2 in mites, 1 in pellitory, 1 in ragweed allergy) met inclusion criteria and were pooled, comparing overall 180 patients treated with active and 155 with placebo. The overall SMD for TSSs resulted [-0.99 (IC -1.41 to -0.57) p<0.001] with a significant interstudy heterogeneity (I 2 = 68%). SMD for grass pollen tablets was [-0.58 (IC -0.89 to -0.27) p<0.001], for mite tablets was [-1.54 (IC -2.07 to -1.02) p<0.001]. The weighted mean RCI was overall -31.69%, for grass pollen tablets -32.14%, for mite tablets -24.27%. Conclusions Indirectly compared to the relative clinical impact of standard pharmacotherapy (antihistamines RCI: -15.0%; antileukotrienes RCI: -6.5%; nasal corticosteroids RCI: -23.5%), carbamylated monomeric allergoids result highly effective in providing symptoms relief in seasonal and perennial allergic rhinoconjunctivitis. This estimation is most likely conservative and apparently reduced by the numerous methodological aspects that differentiate clinical trials on drugs and allergen immunotherapy.

P85 ‐ Asthmatic children and adolescents treated in daily medical practice – results from a 2‐year sublingual allergen immunotherapy (AIT) study with grass pollen tablets

Background The aim of this non-interventional study was to document the impact of a sublingual allergen immunotherapy (AIT) with Oralair 5-grass pollen tablets (Stallergenes, France) on symptom severity (rhinitis, conjunctivitis, asthma), use of symptomatic medication and tolerability in patients with grass pollen-induced allergic rhinoconjunctivitis (RC) over 2 years of routine medical practice treatment. This poster focuses on the subgroup of asthmatic children (4-11 yrs) and adolescents (12-17 yrs).

PD14 ‐ Non‐interventional 2‐year study of sublingual immunotherapy in children and adolescents with allergic rhinoconjunctivitis caused by grass pollen

Background The aim of this non-interventional study was to document the impact of a sublingual allergen immunotherapy (AIT) with Oralair 5-grass pollen tablets (Stallergenes, France) on symptom severity, use of symptomatic medication and tolerability in patients with grass pollen-induced allergic rhinoconjunctivitis (RC) over 2 years of routine medical practice treatment. This poster focuses on the subgroups of children (4-11 yrs) and adolescents (12-17 yrs).